In order to analyze liquid samples, for example bodily fluids such as blood or urine, use is often made of analytical units in which the sample to be analyzed is located on a test field of an analytical element and possibly reacts with one or more reagents in the test field before being analyzed. The optical, in particular photometric, and electrochemical evaluations of analytical elements constitute the most common methods for quickly determining the concentration of analytes in samples. Analytical systems with analytical elements for analyzing samples are generally used in the field of chemical analysis, environmental analysis and, in particular, in the field of medical diagnostics. Analytical elements which are evaluated photometrically or electrochemically are very important, particularly in the field of blood glucose diagnostics from capillary blood.
There are different types of analytical elements. By way of example, substantially square platelets, which are also referred to as slides, are known and have a multilayered test field at their centers. Diagnostic analytical elements designed in the form of a strip are referred to as test strips. The prior art comprehensively describes analytical elements, for example in the documents CA 2311496 A1, U.S. Pat. No. 5,846,837 A or EP 0 821 233 A2, U.S. Pat. No. 6,036,919 A or WO 97/02487.
In capillary gap test elements, the sample liquid is moved in a transport channel (also referred to as a capillary channel or capillary gap) from a sample application location to a sample detection location, at a distance from said application location, using capillary forces in order to undergo a detection reaction at said sample detection location. Capillary gap test elements are known from, for example, CA 2549143 or US 2003/0013147 A1. The capillary channels such as micro-capillaries often have an inner coating of hydrophilic and possibly hydrophobic materials. The liquid transport can be controlled by the hydrophilic and hydrophobic surface properties of the materials contacting the sample liquid.
Analytical tapes with a multiplicity of test fields which are wound up in a cassette and provided for use in an analytical unit are further analytical elements known from the prior art. Such cassettes and analytical tapes are described in, for example, the documents DE 103 32 488 A1, DE 103 43 896 A1, EP 1 424 040 A1, WO 2004/056269 A1 and CA 2506358 A1.
The present invention relates to arbitrarily-shaped analytical elements, such as strip-shaped test elements (e.g. strip-shaped capillary gap test elements) and analytical tapes.
Analytical elements generally have hydrophilic and hydrophobic regions. Herein, the terms “hydrophobic” and “hydrophilic” have the meanings which are generally understood in the art. A hydrophilic surface has a good wettability by water and a hydrophobic surface has a poor wettability by water. The wettability of a surface (and thus, for example, the flow velocity in a capillary having this surface) can be derived from the contact angle α formed between water (or a water-comprising sample) and the surface. If a liquid drop contacts a solid base, two extreme cases can occur. First, complete wetting can occur, in which the adhesion forces are greater than the cohesion forces. Therefore, the sample will spread on the surface of the solid body. Second, incomplete wetting can occur, in which the adhesion forces are (significantly) smaller than the cohesion forces. Therefore, the liquid will contract into a ball-shaped drop.
The wettability and hence, for example, the flow velocity of a liquid sample in a capillary increase as the contact angle α decreases. The filling time for filling a capillary per section increases exponentially with the contact angle. In the case of water-comprising samples, specifying the contact angle of water suffices to characterize the material-specific capillary properties. In this context, the term “hydrophobization” means a change of a surface which effects an increase in the contact angle formed between a liquid water-containing sample and the surface.
So-called “super-hydrophobic” surfaces should be mentioned as extreme cases of hydrophobic surfaces. Such surfaces are completely unwettable and so water drops completely roll off these surfaces. By way of example, such surfaces are used as self-cleaning surfaces.
In the prior art, hydrophilic or hydrophobic surface properties are generated by foils, for example, as a result of impregnating and/or coating processes which use auxiliary substances (e.g. detergents or waxes) suitable in this case. By way of example, hydrophilic or hydrophobic surfaces are produced in a targeted fashion in certain processes in semiconductor production, as a result of which, for example, certain structures can be obtained.
Hydrophilized or hydrophobized surfaces are often used in a targeted fashion also in a crossover field of semiconductor technology and biology, namely in the field of analysis using semiconductor chips (also referred to as “lab on a chip”), in order to produce so-called assays for certain target substances. In the prior art, examples of such chips with functionalized surfaces have been described. See, for example, US 2006/0234269 A1. In the process of making such chips, functionalized multilayered arrangements are used in coating technology which is conventional in semiconductor production, which multilayered arrangements are subsequently modified in a targeted fashion by the action of light, for example by being irradiated by a laser, and are partly ablated again in order to generate the desired structuring of the functionalization. However, such multilayered processes are technically complex, in many cases require complicated clean-room technology and expensive process technology, and are therefore usually unsuitable for mass production of analytical test elements for everyday use.
Other prior art references describe a diagnostic test carrier comprising a carrier layer with a detection layer, which comprises reagents required for determining an analyte in a liquid sample and arranged thereon, and a network which covers the detection layer, is larger than the detection layer and is attached to the detection layer. See, for example, EP 0 821 233 A2. Often, the network formed is hydrophilic, but not capillary-active on its own, and has an inert cover made of a sample-impermeable material which does not cover the sample application area. Such prior art test carriers are typically based on wettable networks which first of all as a whole constitute a possible sample application region. The actual sample application region is subsequently defined by, for example, covers in the form of adhesive tapes. However, such processes are generally complicated in practice, require a number of individual production steps, and in many cases for example only have limited suitability for mass production by means of a roll-to-roll method.
Other prior art references relate to a method for performing analyses, comprising the provision of a device for cultivating microorganisms. The device has an evaluation surface which has hydrophilic, liquid-retaining zones and a hydrophobic, elevated surface between these zones. The hydrophobic surface can be made to be hydrophobic using a number of methods. For example, a thin layer of acrylated silicone or another hydrophobic material can be applied to a polyethylene film which was made to be hydrophilic by a wetting agent being admixed thereto. See, for example, US 2001/0024805 A1.
Yet other prior art references relate to an analytical test element for determining an analyte in the liquid. The test element comprises an inert carrier, an application zone for sample material, a detection zone for determining the analyte and a channel or gap for transporting liquid from the application zone to the detection zone. The test element has a hydrophobically structured surface, at least in one region around the application zone. The structured hydrophobic surface with a lotus effect is produced by coating, saturating, spraying, coextrusion or injection molding. See, for example, WO 2005/054845 A1.
Again other prior art references describe methods for producing an analytical tape for liquid samples. In the process, a multiplicity of test elements are provided on a rollable transportation tape, are spaced apart in the direction of the tape, and are attached to the transportation tape as self-adhesive test labels. The test labels comprise a double-sided adhesive tape and a narrow detection film as a test field which is centered on the upper adhesive layer of the adhesive tape such that lateral adhesive strips of the adhesive layer remain uncovered. A cover layer formed as a fabric is applied thereon, which layer is wider than the detection film and the laterally protruding edges thereof are fixed by the lateral adhesive strips. The protruding edges of the cover layer outside of the detection film are hydrophobized by printing with a water-repellent impregnation and so only a central zone over the detection film can absorb a liquid sample and transport it to the detection film. See, for example, CA 2506358 A1.
The disadvantage of these methods for hydrophobization, known in the prior art, is that auxiliary substances (e.g. detergents, thermal transfer waxes) used for the coating have to be available for years with unchanging quality and with reliable supply conditions. Furthermore, troublesome interactions can occur if hydrophilic and hydrophobic reagents are used at the same time (e.g. interaction of a printed-on hydrophobic thermal transfer wax with a detergent coating of the printed fabric). Moreover, it is often impossible to produce sharp boundaries between hydrophilic and hydrophobically coated regions.
Furthermore, the prior art discloses the use of irradiation with electromagnetic radiation for hydrophobization. In some cases, a hydrophilic layer can be produced from a certain heat-sensitive composition and illuminated by IR radiation, as a result of which the illuminated regions of the layer become more hydrophobic. See, for example, EP 1291173 A1. In other cases, surfaces that have been made hydrophilic as a result of plasma treatments can be converted back into a hydrophobic surface by applying solvents, ultraviolet light or heat. See, for example, WO 98/43739 A2. However, in practice this type of conversion of hydrophilized surfaces into hydrophobic surfaces using the unspecific measures has disadvantages. By way of example, it is possible to ascertain that plasma-treated surfaces only temporarily maintain their high-energy, hydrophilic state. The surface energies are generally significantly increased and therefore not stable in the long-run. However, this means that the surfaces again return to their hydrophobic state over time and this can lead to a significant change in the test element properties. This low stability of the hydrophilization is generally also the reason why the conversion method can be effective, since it is very likely that the disclosed unspecific processes and ingredients such as heat, solvents and UV light would otherwise, in the case of a stably hydrophilized surface, not cause a change into a hydrophobic state.
Furthermore, the methods disclosed in the prior art are complex and costly because preparatory methods have to precede hydrophobization (coating with a heat-sensitive composition/hydrophilization by plasma treatment).
The object of the invention comprises avoiding the disadvantages of the prior art. In particular, it is also an object of the invention to provide a method for producing an analytical element by means of which surface regions of the analytical element can be hydrophobized in a cost-effective and flexible fashion. In particular, the method should be suitable for industrial production, in particular for a roll-to-roll method.